Trial reportJournal of clinical pharmacology2017
Impact of Target-Mediated Elimination on the Dose and Regimen of Evolocumab, a Human Monoclonal Antibody Against Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9).
Trial report in Journal of clinical pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Impact of evolocumab on the pharmacodynamic profiles of clopidogrel in patients with atherosclerotic cardiovascular disease: a randomised, double-blind, placebo-controlled study.EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology · 2023Trial
- Population Pharmacokinetic/Pharmacodynamic Analysis of Alirocumab in Healthy Volunteers or Hypercholesterolemic Subjects Using an Indirect Response Model to Predict Low-Density Lipoprotein Cholesterol Lowering: Support for a Biologics License Application Submission: Part II.Clinical pharmacokinetics · 2019Trial
- Population Pharmacokinetic Analysis of Alirocumab in Healthy Volunteers or Hypercholesterolemic Subjects Using a Michaelis-Menten Approximation of a Target-Mediated Drug Disposition Model-Support for a Biologics License Application Submission: Part I.Clinical pharmacokinetics · 2019Trial
- Small-molecule PCSK9 inhibition enhances BBB amyloid-β clearance and suppresses microglial inflammation in Alzheimer's disease models.Scientific reports · 2026Article
- A surgical window of opportunity trial evaluating the effect of the PCSK9 inhibitor evolocumab on tumoral MHC-I expression and CD8Scientific reports · 2025Article
- Review
- Proprotein convertase subtilisin/kexin type 9 deficiency in extrahepatic tissues: emerging considerations.Frontiers in pharmacology · 2024Review
- Population PK/PD modeling of low-density lipoprotein cholesterol response in hypercholesterolemic participants following administration of bococizumab, a potent anti-PCSK9 monoclonal antibody.CPT: pharmacometrics & systems pharmacology · 2023Article
- Novel and future lipid-modulating therapies for the prevention of cardiovascular disease.Nature reviews. Cardiology · 2023Review
- A case-study of model-informed drug development of a novel PCSK9 anti sense oligonucleotide. Part 1: First time in man to phase II.CPT: pharmacometrics & systems pharmacology · 2022Article
- Combined Semi-mechanistic Target-Mediated Drug Disposition and Pharmacokinetic-Pharmacodynamic Models of Alirocumab, PCSK9, and Low-Density Lipoprotein Cholesterol in a Pooled Analysis of Randomized Phase I/II/III Studies.European journal of drug metabolism and pharmacokinetics · 2022Article
- Application of quantitative protein mass spectrometric data in the early predictive analysis of target engagement by monoclonal antibodies.Clinical and translational science · 2022Article
- Musculoskeletal Adverse Events Associated with PCSK9 Inhibitors: Disproportionality Analysis of the FDA Adverse Event Reporting System.Cardiovascular therapeutics · 2022Article
- Hepatic Sensing Loop Regulates PCSK9 Secretion in Response to Inhibitory Antibodies.Journal of the American College of Cardiology · 2021Article
- Influence of Renal Function on Evolocumab Exposure, Pharmacodynamics, and Safety.Clinical pharmacology in drug development · 2019 · on this mapArticle
- Influence of Antigen Mass on the Pharmacokinetics of Therapeutic Antibodies in Humans.Clinical pharmacokinetics · 2019Review
- Lack of ethnic differences in the pharmacokinetics and pharmacodynamics of evolocumab between Caucasian and Asian populations.British journal of clinical pharmacology · 2019Article
- A Phase 1, Randomized, Double-Blind, Single-Dose, Placebo-Controlled Safety, Tolerability, And Pharmacokinetic/Pharmacodynamic Study Of Evolocumab In Healthy Chinese Subjects.Clinical pharmacology : advances and applications · 2019Article
- Tutorial on Monoclonal Antibody Pharmacokinetics and Its Considerations in Early Development.Clinical and translational science · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding the pharmacokinetic (PK) and pharmacodynamic (PD) relationship of a therapeutic monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9) exhibiting target-mediated drug disposition (TMDD) is critical for selecting optimal dosing regimens. We describe the PK/PD relationship of evolocumab using a mathematical model that captures evolocumab binding and removal of unbound PCSK9 as well as reduction in circulating low-density lipoprotein cholesterol (LDL-C). Data were pooled from 2 clinical studies: a single-dose escalation study in healthy subjects (7-420 mg SC; n = 44) and a multiple-dose escalation study in statin-treated hypercholesterolemic patients (14 mg weekly to 420 mg monthly [QM] SC; n = 57). A TMDD model described the time course of unbound evolocumab concentrations and removal of unbound PCSK9. The estimated linear clearance and volume of evolocumab were 0.256 L/day and 2.66 L, respectively, consistent with other monoclonal antibodies. The time course of LDL-C reduction was described by an indirect response model with the elimination rate of LDL-C being modulated by unbound PCSK9. The concentration of unbound PCSK9 associated with half-maximal inhibition (IC
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.